CYP2C19
CPT Code 81225
Order Code C603
Sample Type EDTA Whole Blood Tube Type Lavender Top
Types of clopidogrel (Plavix®) metabolizers based
on the CYP2C19 genotype:
• Poor metabolizer
• Intermediate metabolizer
• Extensive/Normal metabolizer
• Ultra-rapid metabolizer
Population statistics for poor metabolizers1-3:
• Asians (14-20%)
• African American (4%)
• Caucasian (2-4%)
Description
CYP2C19 is a member of the cytochrome P450 family of enzymes
involved in the metabolism and bioactivation of drugs. In particular,
CYP2C19 is integral for the generation of the active form of
clopidogrel (Plavix®), which is prescribed in a prodrug form. This
prodrug is converted by CYP2C19 to the active form in the liver.
Several variants of CYP2C19 have been identified which have
an impact on its ability to metabolize drugs. The main CYP2C19
alleles include the non-functional alleles *2 and *3, as well as the
hyperactive *17 allele.
Clinical Use
Sample Type
The CYP2C19 test requires one EDTA whole blood sample. If
performing other tests that require an EDTA whole blood sample,
they should be collected in a separate lavender top tube.
Testing Frequency
The CYP2C19 test should only be performed once on an individual
as it is a genetic test.
Commercial Insurance or Medicare Coverage
Coverage guidelines, also known as NCD (National Coverage
Determination) or LCD (Local Coverage Determination) have been
established or posted by CMS (Medicare & Medicaid). Limited
information has been posted by the majority of the larger Carriers
(Aetna, United HealthCare, Cigna, Blues). Medical necessity and
specificity of diagnosis should be provided when ordering this test.
Understanding Medical Necessity
The following ICD-9 codes for CYP2C19 are listed as a convenience
for the ordering physician. The ordering physician should report
the diagnosis code that best describes the reason for performing
the test and provide the 4th and 5th ICD-9 digit as appropriate.
Diagnosis
Diagnosis Code
CYP2C19 testing may be performed on individuals who are
candidates for or are currently taking clopidogrel (Plavix®), or those
who have a family history of clopidogrel (Plavix®) inefficacy.
Pure Hypercholesterolemia
272.0
Unspec. Hyperlipidemia
272.4
Clinical Significance
Mixed Hyperlipidemia
272.2
Coronary atherosclerosis of native
coronary artery
414.01
•In 2010, the FDA announced a boxed warning for clopidogrel
(Plavix®) to alert patients and physicians to the drug’s inefficacy
in individuals who cannot metabolize the drug to its active form2.
•Poor metabolizers (loss of CYP2C19 activity) have 2X the risk
of having a subsequent adverse cardiac event while receiving
treatment with clopidogrel after a myocardial infarction4.
•Ultra-rapid metabolizers (increased CYP2C19 activity) have a
reduced risk of major adverse cardiac events while being treated
with clopidogrel5, but are at an increased risk of bleeding6.
6701 Carnegie Ave. | Suite 500 | Cleveland, OH 44103 | p 866.358.9828 | f 866.869.0148 | www.clevelandheartlab.com
Treatment Considerations
These treatment considerations are for educational purposes only. Specific treatment plans should be provided and
reviewed by the treating practitioner.
Phenotype
Genotype
Interpretation
Poor
Metabolizer
Two non-functional
alleles
(*2/*2 or *2/*3
or *3/*3)
Poor metabolizers do not effectively convert the
drug to its active metabolite and exhibit poor
anti-platelet responsiveness.
Intermediate metabolizers convert the drug
to an active metabolite at a slower rate than
a normal metabolizer and exhibit decreased
responsiveness to the drug.
Treatment Consideration
Consider a higher dosage
of clopidogrel (Plavix®) or an
alternative therapy.
Intermediate
Metabolizer
One WT and one
non-functional allele
(WT/*2 or WT/*3)
Normal (Extensive)
Metabolizer
No mutations
(WT/WT)
Normal metabolizers effectively convert the drug
to an active metabolite.
Consider a standard dosage of
clopidogrel (Plavix®).
One WT and one
hyperactive allele or
2 hyperactive alleles
(WT/*17 or *17/*17)
Ultra-rapid metabolizers convert a higher
percentage of the drug to an active metabolite,
and have a greater therapeutic response to the
drug compared to normal metabolizers. Ultrarapid metabolizers may produce an adequate
platelet response even when lower than normal
doses of the drug are used, and are at increased
risk of bleeding.
Consider a standard or reduced
dosage of clopidogrel (Plavix®)
and monitoring the patient for
potential bleeding.
The metabolizer status is uknown for individuals
with this genotype.
Consider an alternative therapy.
Ultra-Rapid
Metabolizer
Unknown
One non-functional
allele and one
hyperactive allele
(*2/*17 or *3/*17)
The Cleveland HeartLab assay identifies the non-functional alleles *2 and *3, and the ultra-rapid allele *17 of the CYP2C19 gene.
The presence of less common alleles can not be ruled out by this test.
References
1. Desta Z et al. Clinical significance of the cytochrome P450 2C19 genetic polymorphism. Clin Pharmacokinet. 2002; 41: 913-958.
2. Product Information for Plavix (Sanofi/Aventis US). Label Information, approved Feb 2011. www.accessdata.fda.gov/drugsatfda_docs/label/2011/020839s052lbl.pdf. Accessed June 27, 2013.
3. Shuldiner AR et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA. 2009; 302: 849-857.
4. Mega JL et al. Cytochrome P-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009; 360: 354-362.
5. Li Y et al. The gain-of-function variant allele CYP2C19*17: A double-edged sword between thrombosis and bleeding in clopidogrel-treated patients. J Thromb Haemost. 2012; 10: 199-206.
6. Sibbing D et al. Cytochrome 2C19*17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in clopidogrel-treated patients with coronary stent placement. Circulation. 2010; 121:
512-518.
6701 Carnegie Ave. | Suite 500 | Cleveland, OH 44103 | p 866.358.9828 | f 866.869.0148 | www.clevelandheartlab.com
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